The ontogeny of mammalian exocrine pancreatic function and the factors controlling this process will be elucidated by studies of the pancreas of the fetal and neonatal rat. The term fetal rat pancreas, although structurally mature, is functionally immature, in vitro. The pattern of development of function of the rat pancreas will be characterized by measuring the secretion of exportable protein from fragments prepared from immature rat pancreas after stimulation with secretagogues (e.g., carbamycholine, pancreozymin, the calcium ionophore, A23187). Since morphological maturation preceeds functional maturation, emphasis will be placed on agents such as hormones, drugs, and diet that may stimulate or inhibit morphological (and thus functional) maturation. Functional maturation will be determined by the measurement of the secretion of amylase, trypsiongen and chymotrypsinogen. Since the accumulation of exportable protein is nonparallel in the fetal pancreas, we will determine whether the ability to secrete such proteins is also developed in a nonparallel fashion. The role of critical perinatal events such as birth and first feeding in inducing maturation of function will be elucidated. After attempts have been made to induce or inhibit maturation, specific activities of exportable proteins will be determined and secretory studies will be performed and light and electron microscopy o will be performed. Since cyclic nucleotides especially cyclic GMP have been implicated in stimulus-secretion coupling in the pancreatic acinar cell, the development of the ability of the exocrine pancreas to generate cyclic nucleotides will likewise be elucidated. It will be determined whether functional maturation and the ability to generate cyclic GMP and cyclic AMP develop synchronously. Isolated acinar cells will be prepared from inmmature pancreas and it will be determined whether inhibitors are responsible for the delay in maturation of function seen in this model. These studies will help elucidate the control of maturation of function and intracellular effectors in the mammalian exocrine pancreas.